1. Field of the Invention
This invention relates to a method for administering analgesics, antipyretics and anti-inflammatory agents by rectal delivery. It particularly relates to a method for enhancing and prolonging the rate of absorption of such rectally delivered medicinal agents from the rectal compartment to the bloodstream. This invention also relates to improved rectal suppository dosage forms used in the practice of such method.
2. Description of Related Art
One known method of drug administration is accomplished by the incorporation of a medically active substance in a "suppository," which, generally speaking, is a medicated solid unit dosage form typically intended for use in the rectum, vagina, and to a lesser extent, in the urethra. Rectal suppositories usually employ vehicles that melt or soften at body temperatures so that the drug may be released for use. Drugs administered in suppository form are administered for either local or systemic therapeutic effect. The action of the drug is dependent on the nature of the drug, its concentration, and its rate of absorption. Although rectal suppositories are commonly used for the treatment of constipation and hemorrhoids, that is, for local effect, such rectal suppositories are also administered rectally for systemic action. A wide variety of drugs may be rectally administered, as by the use of suppositories, including, for example, analgesics, antispasmodics, sedatives, tranquilizers, and antibacterial agents.
Rectal drug administration has many advantages over other routes of drug administration, such as oral administration and parenteral administration. For example, many drug substances that are given orally undergo inactivation in the stomach because of the acidic, enzymatic content of the stomach or the drug may be subject to digestive attack in the gut and/or to microbial degradation in the lower gut. Oral administration of drugs also directs all of the absorbed substances through the liver where they can be inactivated or reduced in effectiveness.
Rectal administration overcomes wholly, or in part, these known disadvantages of oral drug administration. Rectal drug administration also has advantages over parenteral administration. For example, rectal drug administration does not require highly trained personnel required for parenteral administration and also represents significantly less discomfort or hazard to the patient.
In view of the known disadvantages of oral and parenteral drug administration, drug administration by rectal delivery enables many drugs to be absorbed from the anorectal area, and yet retain their therapeutic value. The lower hemorrhoidal vein, surrounding the colon and rectum, enters the inferior vena cava and thereby bypasses the liver. Therefore, drugs are absorbed directly into the general circulation when rectally administered. For further background on rectal delivery of drugs, reference is made herein to an article entitled "Rectal Administration of Drugs" by N. Senior, "Advances in Pharmaceutical Sciences," edited by Bean, Beckett, and Corlass, Volume IV, Academic Press (1974) and to Chapter 8, "Suppositories", by Joachim Anschel and Herbert A. Lieberman, Lachman and Lieberman "Theory and Practice of Industrial Pharmacy", Lea and Febiger (1976).
Despite the known advantages of rectal administration of drugs, the rectal administration of drugs is not totally without problems. Many rectally administered drugs are poorly absorbed while others are slowly absorbed and, if so, are often inactivated or degraded while still in the rectal compartment. Generally, analgesics, antipyretics and anti-inflammatory agents which are rectally administered in the form of a suppository are rapidly absorbed with the result that the physiological effects only last for a short duration. Furthermore, the remarkably high blood levels in the early phase often cause undesirable side effects such as headache and vomiting. It would therefore be highly advantageous if rectally administered medicinal substances such as the analgesics, antipyretics and anti-inflammatory agents could have their rate of absorption from the rectal compartment to the bloodstream enhanced. Prolonging the rectal absorption of these drugs results in higher bioavailability and decreases or eliminates the side effects by suppressing the high blood levels in the early phase and sustaining the blood levels for longer duration.